OPEN Foundation

OPEN Foundation

Is Ecstasy an “Empathogen”? Effects of ±3,4-Methylenedioxymethamphetamine on Prosocial Feelings and Identification of Emotional States in Others

December 15, 2010 / MDMA, Other subjects, Papers, Psychology, Psychopharmacology, Publications / By / , ,

Abstract

Background: Users of MDMA (“ecstasy”) report that the drug produces unusual psychological effects, including increased empathy and prosocial feelings. These “empathogenic” effects are cited as reasons for recreational ecstasy use and also form the basis for the proposed use of MDMA in psychotherapy. However, they have yet to be characterized in controlled studies. Here, we investigate effects of MDMA on an important social cognitive capacity, the identification of emotional expression in others, and on socially relevant mood states.

Methods: Over four sessions, healthy ecstasy-using volunteers (n = 21) received MDMA (.75, 1.5 mg/kg), methamphetamine (METH) (20 mg), and placebo under double-blind, randomized conditions. They completed self-report ratings of relevant affective states and undertook tasks in which they identified emotions from images of faces, pictures of eyes, and vocal cues.

Results: MDMA (1.5 mg/kg) significantly increased ratings of feeling “loving” and “friendly”, and MDMA (.75 mg/kg) increased “loneliness”. Both MDMA (1.5 mg/kg) and METH increased “playfulness”; only METH increased “sociability”. MDMA (1.5 mg/kg) robustly decreased accuracy of facial fear recognition relative to placebo.

Conclusion: The drug MDMA increased “empathogenic” feelings but reduced accurate identification of threat-related facial emotional signals in others, findings consistent with increased social approach behavior rather than empathy. This effect of MDMA on social cognition has implications for both recreational and therapeutic use. In recreational users, acute drug effects might alter social risk-taking while intoxicated. Socioemotional processing alterations such as those documented here might underlie possible psychotherapeutic benefits of this drug; further investigation of such mechanisms could inform treatment design to maximize active components of MDMA-assisted psychotherapy.

Bedia, G., Hymana, D., & de Wit, H. (2010). Is Ecstasy an “Empathogen”? Effects of ±3,4-Methylenedioxymethamphetamine on Prosocial Feelings and Identification of Emotional States in Others. Biological Psychiatry, 68(12), 1134-1140. http://dx.doi.org/10.1016/j.biopsych.2010.08.003
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Lack of effect of sublingual salvinorin A, a naturally occurring kappa opioid, in humans: a placebo-controlled trial

December 8, 2010 / Other subjects, Papers, Psychopharmacology, Publications, Salvia / Salvinorin A / By / , , , , , ,

Abstract

Rationale: Salvinorin A (SA) is a highly selective kappa opioid receptor agonist and the putative psychoactive compound in Salvia divinorum (SD), an increasingly abused hallucinogenic plant.

Objectives: The objectives of this study were to characterize the physiological and subjective effects of SA versus placebo and measure drug and metabolite levels.

Methods: Sublingual SA doses up to 4 mg were administered in dimethyl sulfoxide/polyethylene glycol 400 solution to eight SD-experienced subjects using a placebo-controlled ascending-dose design.

Results: No dose of SA produced significantly greater physiological or subjective effects than placebo. Furthermore, effects did not resemble reported “typical” effects of smoked SD. SA was detectable in plasma and urine, but was, in most cases, below the reliable limit of quantification (0.5 ng/mL).

Cconclusions: Our results suggest that the sublingual bioavailability of SA is low. Higher doses, alternate formulations, or alternate routes of administration will be necessary to study the effects of SA in humans.

Mendelson, J. E., Coyle, J. R., Lopez, J.C., Baggott, M. J., Flower, K., Everhart, E. T., … Cohen, B. M. (2010). Lack of effect of sublingual salvinorin A, a naturally occurring kappa opioid, in humans: a placebo-controlled trial. Psychopharmacology, 214(4), 933-939. http://dx.doi.org/10.1007/s00213-010-2103-5
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Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum

December 3, 2010 / Other subjects, Papers, Psychology, Psychopharmacology, Publications, Safety, Salvia / Salvinorin A / By / , , , ,

Abstract

Salvinorin A is a potent, selective nonnitrogenous kappa opioid agonist and the known psychoactive constituent of Salvia divinorum, a member of the mint family that has been used for centuries by Mazatec shamans of Mexico for divination and spiritual healing. S. divinorum has over the last several years gained increased popularity as a recreational drug. This is a double-blind, placebo controlled study of salvinorin A in 4 psychologically and physically healthy hallucinogen-using adults. Across sessions, participants inhaled 16 ascending doses of salvinorin A and 4 intermixed placebo doses under comfortable and supportive conditions. Doses ranged from 0.375 μg/kg to 21 μg/kg. Subject-rated drug strength was assessed every 2 min for 60 min after inhalation. Orderly time- and dose-related effects were observed. Drug strength ratings peaked at 2 min (first time point) and definite subjective effects were no longer present at approximately 20 min after inhalation. Dose-related increases were observed on questionnaire measures of mystical-type experience (Mysticism Scale) and subjective effects associated with classic serotonergic (5-HT2A) hallucinogens (Hallucinogen Rating Scale). Salvinorin A did not significantly increase heart rate or blood pressure. Participant narratives indicated intense experiences characterized by disruptions in vestibular and interoceptive signals (e.g., change in spatial orientation, pressure on the body) and unusual and sometimes recurring themes across sessions such as revisiting childhood memories, cartoon-like imagery, and contact with entities. Under these prepared and supportive conditions, salvinorin A occasioned a unique profile of subjective effects having similarities to classic hallucinogens, including mystical-type effects.

Johnson, M. W., Maclean, K.A., Reissig, C. R., Prisinzano, T. E., & Griffiths, R. R. (2010). Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum. Drug and Alcohol Dependence, 115(1-2), 150-155. http://dx.doi.org/10.1016/j.drugalcdep.2010.11.005

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Investigating the Mechanisms of Hallucinogen-Induced Visions Using 3,4-Methylenedioxyamphetamine (MDA): A Randomized Controlled Trial in Humans

December 2, 2010 / Other subjects, Other substances, Papers, Psychology, Publications / By / , , , , ,

Abstract

Background: The mechanisms of drug-induced visions are poorly understood. Very few serotonergic hallucinogens have been studied in humans in decades, despite widespread use of these drugs and potential relevance of their mechanisms to hallucinations occurring in psychiatric and neurological disorders.

Methodology/Principal Findings: We investigated the mechanisms of hallucinogen-induced visions by measuring the visual and perceptual effects of the hallucinogenic serotonin 5-HT2AR receptor agonist and monoamine releaser, 3,4-methylenedioxyamphetamine (MDA), in a double-blind placebo-controlled study. We found that MDA increased self-report measures of mystical-type experience and other hallucinogen-like effects, including reported visual alterations. MDA produced a significant increase in closed-eye visions (CEVs), with considerable individual variation. Magnitude of CEVs after MDA was associated with lower performance on measures of contour integration and object recognition.

Conclusions/Significance: Drug-induced visions may have greater intensity in people with poor sensory or perceptual processing, suggesting common mechanisms with other hallucinatory syndromes. MDA is a potential tool to investigate mystical experiences and visual perception.

Baggott, M. J., Siegrist, J. D., Galloway, G. P., Robertson, L. C., Coyle, J. R., & Mendelson, J. E. (2010). Investigating the Mechanisms of Hallucinogen-Induced Visions Using 3,4-Methylenedioxyamphetamine (MDA): A Randomized Controlled Trial in Humans. PLoS ONE, 5(12), 1-13. http://dx.doi.org/10.1371/journal.pone.0014074
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Evolution and origins of the Mazatec hallucinogenic sage, Salvia divinorum (Lamiaceae): a molecular phylogenetic approach

December 2, 2010 / Ethnobotany, Other subjects, Papers, Publications, Salvia / Salvinorin A / By / , ,

Abstract

Salvia divinorum Epl. & Játiva-M. (Lamiaceae) is a potent hallucinogenic plant that is classified within Salvia subgenus Calosphace, section Dusenostachys, and hypothesized to be an interspecific hybrid. It is of ethnobotanical significance due to its employment in traditional healing ceremonies by the Mazatecs of Oaxaca, Mexico, and due to its unique pharmacology—a highly selective, non-nitrogenous, j-opioid receptor agonist. In order to test its phylogenetic position and putative hybridity, we sequenced multiple DNA regions (ITS, trnL-trnF, and psbA-trnH) of 52 species—representing the major lineages of subgenus Calosphace—and six accessions of S. divinorum. Our molecular phylogenetic results suggest that S. divinorum should not be classified within Dusenostachys and that it is not a hybrid. Additionally, we determine that the closest known relative of this psychoactive Mexican sage is S. venulosa, a rare endemic of Colombia.

Jenks, A. A., Walker, J.B., Kim, S. C. (2010). Evolution and origins of the Mazatec hallucinogenic sage, Salvia divinorum (Lamiaceae): a molecular phylogenetic approach. Journal of Plant Research, 124(5), 593-600. http://dx.doi.org/10.1007/s10265-010-0394-6
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Ayahuasca, Salutogenesis and the Need for „Ecological“ Approaches

November 14, 2010 / Ayahuasca, Other disciplines, Other subjects, Papers, Publications, Spirituality / By /

Abstract

In Western science, extraordinary or visionary states of consciousness are traditionally discussed mainly in terms of psychopathology, that is, in the sense of mental disease. This applies even more when they are associated with psychoactive substances such as the herbal decoction Ayahuasca, which are generally called “hallucinogens” with the connotation “not objective, unreal”. However, responsible work with psychoactive herbal decoctions like Ayahuasca – similar to many forms of meditation – has salutogenic potential, i.e. it can enhance physical, mental and spiritual health by calling into play what is referred to as “participating consciousness”. Rigid feeling, thought, and behavioural patterns can unclench, the self can rearrange itself and develop its inner and outer resources more deeply.

The thesis of this article is that for an adequate understanding of these processes, the familiar “linear” thinking no longer suffices, rather, an “ecology of mind” is needed (Bateson 1972), i.e. less divisive, less objectifying explanations which also do not exclude the fundamental paradoxes of human existence. Of course, such approaches occasionally need some getting used to.

In the following, a few basic elements of the ecological approach will be explained (chapter 2). Chapter 3 will then analyze whether or not and to what extent this approach can explain extraordinary states of consciousness better than traditional, linear thinking.

Friczewski, F. (2010). Ayahuasca, Salutogenesis and the Need for „Ecological“ Approaches.

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Psychobiology of Drug-Induced Religious Experience: From the Brain 'Locus of Religion' to Cognitive Unbinding

November 13, 2010 / Ayahuasca, LSD, Mushrooms / Psilocybin, Mystical experiences, Neuroscience, Papers, Psychology, Publications, Religious studies, Spirituality / By / ,

Abstract

The recent interest in the psychopharmacological underpinnings of religious experiences has led to both the laboratory characterizations of drug-induced mystical events and psychobiological models of religious experiences rooted in evolution and fitness. Our examination of this literature suggests that these theories may be congruent only within more modern religious and cultural settings and are not generalizable to all historical beliefs, as would be expected from an evolutionarily conserved biological mechanism. The strong influence of culture on the subjective effects of drugs as well as religious thoughts argues against the concept of a common pathway in the brain uniquely responsible for these experiences. Rather, the role of personal beliefs, expectations and experiences may interject bias into the interpretation of psychoactive drug action as a reflection of biologically based religious thought. Thus, psychobiological research proposing specific brain mechanisms should consider anthropological and historical data to address alternative explanations to the “fitness” of religious thought. A psychobiological model of the religious experience based on the concept of cognitive unbinding seems to accommodate these data better than that of a specific brain locus of religion.

Nencini, P., & Grant, G. A. (2010). Psychobiology of Drug-Induced Religious Experience: From the Brain ‘Locus of Religion’ to Cognitive Unbinding. Substance Use & Misuse, 45(13), 2130–2151. http://dx.doi.org/10.3109/10826081003713803
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Methodology for and the determination of the major constituents and metabolites of the Amazonian botanical medicine ayahuasca in human urine

October 26, 2021 / Ayahuasca, Papers, Publications, Safety, Toxicology / By / , , , ,

Abstract

Ayahuasca, also known as caapi or yage among various South American groups, holds a highly esteemed and millennia-old position in these cultures’ medical and religious pharmacopeia. There is now an increasing interest in the potential for modern medical applications of ayahuasca, as well as concerns regarding its increasing potential for abuse. Toxicological and clinical research to address these issues will require information regarding its metabolism and clearance. Thus, a rapid, sensitive and specific method for characterization and quantitation of the major constituents and of the metabolites of ayahuasca in urine is needed. The present research provides a protocol for conducting such analyses. The characteristics of the method, conducted by sample dilution and using HPLC–electrospray ionization (ESI)–selected reaction monitoring (SRM)–tandem mass spectrometry, are presented. The application of the analytical protocol to urine samples collected from three individuals that were administered ayahuasca has also been demonstrated. The data show that the major metabolite of the hallucinogenic component of ayahuasca, N,N-dimethyltryptamine (DMT), is the corresponding N-oxide, the first time this metabolite has been described in in vivo studies in humans. Further, very little DMT was detected in urine, despite the inhibition of monoamine oxidase afforded by the presence of the harmala alkaloids in ayahuasca. The major harmala alkaloid excreted was tetrahydroharmine. Other excretion products and metabolites were also identified and quantified. The method described would be suitable for use in further toxicological and clinical research on ayahuasca.

McIlhenny, E. H., Riba, J., Barbanoj, M. J., Strassman, R., & Barker, S. A. (2011). Methodology for and the determination of the major constituents and metabolites of the Amazonian botanical medicine ayahuasca in human urine. Biomedical Chromatography, 25(9), 970-984. 10.1002/bmc.1551
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14 May - Psychedelics & Psychosis with Phoebe Friesen, Dirk Corstens and Chelsea Rose

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